Abstract: Selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine and paroxetine are prescribed to relieve clinical depression and a variety of other disorders. Recently tardive dyskinesia, as well as other movement disorders, have been found to be a clinical side effect of SSRIs. In light of these emerging side effects, we asked if motor neurons were affected by SSRI. Motor neurons were challenged with fluoxetine and paroxetine at clinically relevant doses as well as at lesser and greater doses. Ethanol was used as a negative control and another group of cells was left untreated. As expected, in alcohol-treated cells, there was significant decrease in cell survival and neurite outgrowth. In untreated cells there was no effect in either cell survival or neurite outgrowth. In fluoxetine-treated motor neurons there was ~52% cell death while in paroxetine-treated cells there was 14% cell survival and both SSRIs caused significant loss of the percentage of neurite-bearing cells. Both SSRIs decreased cell survival in a dose-dependent manner. This study is provocative enough to call for further in vivo studies.

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